Tuberculosis and Malaria are two of the world's deadliest diseases, with more than two million deaths worldwide in 2013, most of them in sub-Saharan Africa, South-East Asia and Western Pacific regions. Plasmodium falciparum has for some time been developing resistance against known antimalarial drugs, and therefore new drugs are urgently needed. Chloroquine was the first drug produced on a large scale for treatment and prevention of malaria infection. Chloroquine has activity against the blood stages of Plasmodium ovale, P. malariae, and susceptible strains of P. vivax and P. falciparum. Widespread resistance in most malaria-endemic countries has led to a continual decline in its use for the treatment of P. falciparum, although it remains effective for treatment of P. ovale, P. malariae, and, in most regions, P. vivax. 
Tuberculosis (TB) is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent, Mycobacterium tuberculosis (Mtb). Standard antimycobacterial drugs (isoniazid, rifampicin, pyrazidamide, ethambutol, streptomycin) have been used for decades, and resistance to the medicines is also widespread. If a patient is unable to tolerate isoniazid, or if isoniazid-resistant TB is present, rifampicin, ethambutol, and pyrazidamide are usually used for 18 months. If rifampicin-resistant TB is present, the regimen usually consists of isonizaid, ethambutol, and pyrazidamide for 18 months. If there is resistance to both isoniazid and rifampicin, the disease is very difficult to treat. Disease strains that are resistant to a single anti-TB drug have been documented in every country surveyed. In some cases more severe drug resistance can develop. Extensively drug-resistant TB, XDR-TB, is a form of multi-drug resistant tuberculosis (MDR-TB) that responds to even fewer available medicines, including the most effective second-line anti-TB drugs. About 480,000 people developed MDR-TB in the world in 2013. More than half of these cases were in India, China and the Russian Federation. It is estimated that about 9.6% of MDR-TB cases had XDR-TB. Hence, the search for new antitubercular drugs is a priority so as to overcome the problem of drug resistance and to finally eradicate TB.
The marine sponge metabolite (−)-8,15-diisocyano-11(20)-amphilectene 1 (see FIG. 1) was first reported by Faulkner et al. from Hymeniacidon amphilecta in 1978, and has been shown subsequently to exhibit potent in vitro anti-infective activity. Several structurally related natural products as well as a small number of synthetic analogs prepared from diisocyanide 1 also exhibit antimalarial and antimycobacterial potential. While comparison among their activities reveals that the biological activity is generally dependent on the presence of the isocyanide functionality, the structural features of the carbon backbone and the location of the isocyanide groups also seem to play a pivotal role. Notwithstanding, the observation that a plethora of sponge-derived isocyanide-, isothiocyanate-, isocyanate-, and formamide-containing diterpenoids based on amphilectane, cycloamphilectane, isocycloamphilectane, and isoneoamphilectane skeletons are often active (usually in the low nanomolar range), suggests that the biological activity does not depend strictly on the presence of the isocyanide functionality. This observation implies that the metabolite's carbon skeleton can also modulate biological activity.
As part of the inventor's drug discovery program in search of new agents for the treatment of Malaria and Tuberculosis, we became interested in the synthesis of a limited number of amphilectane-based isothiocyanate and isoselenocyanate diterpenes for biological evaluation. Of the two classes of congeneric compounds, organic isoselenocyanates are of particular interest since so far they have received much less attention compared to their sulfur and oxygen analogs. diisocyanide 1 was targeted as a suitable starting material, a well-known antimalarial and antimycobacterial pharmacophore which contains both a rigid amphilectane skeleton and two isocyanide “handles” with potential for further synthetic elaboration. It was anticipated that comparison among the biological activities exhibited by the strickly related amphilectane analogs with those of 1 would reveal definite structure-activity relationships. While the isothiocyanate moiety is found in many natural products only two isothiocyanate-containing amphilectane diterpenoids with antiplasmodial activity have been documented. Remarkably, no studies assessing the potential antiplasmodial or antimycobacterial properties of isoselenocyanate-containing compounds (synthetic or natural) have been reported so far.